Chen Ya-Juan, Li Hui-Min, Lu Wei, Qing Chen
School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Nature Products, Kunming Medical University, Kunming 650500, Yunnan Province, China.
Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Dec;21(6):1454-9. doi: 10.7534/j.issn.1009-2137.2013.06.016.
This study was aimed to investigate the effect of arsenic trioxide (As2O3) on proliferation and cell cycle of human Burkitt lymphoma cells and its related molecular mechanism, so as to provide experimental evidence for treatment of Burkitt lymphoma with As2O3. Human Burkitt lymphoma cell line Namalwa was used as the model, the effect of As2O3 on cell proliferation, cell cycle and apoptosis, as well as the expression of cell cycle modulation related genes, including mRNA and protein level, were detected by MTT method, flow cytometry, real-time quantitative PCR (RQ-PCR) and Western blot, respectively. The results showed that the As2O3 inhibited significantly the growth and proliferation of Namalwa cells in concentration-and time-dependent manner. The As2O3 arrested obviously cell cycle of Namalwa cells in G1 phase, and showed significant concentration-effect relationship. The As2O3 induced the apoptosis of Namalwa cells in concentration-and time-dependent manner, downregulated the expression of the important driving genes of cell cycle including Cyclin E and CDK2 in mRNA and protein level, upregulated the expression of the important inhibiting gene of cell cycle-P21 in mRNA and protein level in concentration-dependent manner. It is concluded that As2O3 inhibits significantly the growth and proliferation of Namalwa cells, and the effect was closely relates with its inducing the apoptosis and blocking the cell cycle of Namalwa. The action of blocking cell cycle is closely associated with its downregulating the expression of driving genes of cell cycle-Cyclin E and CDK2, upregulating the expression of the inhibiting gene of cell cycle-P21.
本研究旨在探讨三氧化二砷（As2O3）对人伯基特淋巴瘤细胞增殖及细胞周期的影响及其相关分子机制，为As2O3治疗伯基特淋巴瘤提供实验依据。以人伯基特淋巴瘤细胞系Namalwa为模型，分别采用MTT法、流式细胞术、实时定量PCR（RQ-PCR）和蛋白质印迹法检测As2O3对细胞增殖、细胞周期和凋亡的影响，以及细胞周期调控相关基因在mRNA和蛋白质水平的表达。结果显示，As2O3能以浓度和时间依赖性方式显著抑制Namalwa细胞的生长和增殖。As2O3能明显使Namalwa细胞的细胞周期阻滞于G1期，并呈现显著的浓度效应关系。As2O3能以浓度和时间依赖性方式诱导Namalwa细胞凋亡，在mRNA和蛋白质水平下调细胞周期重要驱动基因Cyclin E和CDK2的表达，在浓度依赖性方式下在mRNA和蛋白质水平上调细胞周期重要抑制基因P21的表达。结论：As2O3能显著抑制Namalwa细胞的生长和增殖，其作用与其诱导Namalwa细胞凋亡和阻滞细胞周期密切相关。细胞周期阻滞作用与其下调细胞周期驱动基因Cyclin E和CDK2的表达、上调细胞周期抑制基因P21的表达密切相关。
